Purpose: The purpose of this controlled prospective clinical study was to compare cemented and screw-retained implant-supported single-tooth crowns followed for 4 years following prosthetic rehabilitation with respect to peri-implant marginal bone levels, peri-implant soft tissue parameters, and prosthetic complications. Materials and Methods: Twelve consecutive patients were selected from a patient population attending the Implantology Department at the University of Padova. They all presented with single-tooth bilateral edentulous sites in the canine/premolar/molar region with adequate bone width, similar bone height at the implant sites, and an occlusal scheme that allowed for the establishment of identical occlusal cusp/fossa contacts. Each patient received 2 identical implants (1 in each edentulous site). One was randomly selected to be restored with a cemented implant-supported single-tooth crown, and the other was restored with a screw-retained implant-supported singletooth crown. Data on peri-implant marginal bone levels and on soft tissue parameters were collected 4 years after implant placement and analyzed to determine whether there was a significant difference with respect to the method of retention (cemented versus screw-retained). Results: All patients completed the study. All 24 implants survived, resulting in a cumulative implant success rate of 100%. Statistical analysis revealed no significant differences between the 2 groups with respect to peri-implant marginal bone levels and soft tissue parameters. Discussion: The data obtained with this study suggested that the choice of cementation versus screw retention for single-tooth implant restorations is likely not based on clinical results but seems to be based primarily on the clinician's preference. Conclusions: Within the limitations of this study, the results indicate that there was no evidence of different behavior of the peri-implant marginal bone and of the peri-implant soft tissue when cemented or screw-retained single-tooth implant restorations were provided for this patient population.